Search PubMed⌕ Search

Biomedical subjects

L M Grover

Publications and source records attributed to L M Grover.

28 records · Page 2Linked to original sources

An integrated multielectrode electrophysiology system.

An integrated system for recording and analyzing electrophysiological data from multiple channels is described. The system uses an MS-DOS microcomputer, a 16-channel amplifier, and multiple-tipped electrode arrays designed for use in intact and slice preparations. The system is designed for applications where the collection and analysis of multiple-channel electrophysiological data is desirable, including the construction of current source density (CSD) profiles from field potential data. The software incorporates on-line averaging, CSD and freeze-frame capabilities to guide the experiment in progress. Additional off-line analyses include multiple unit activity, power spectra, and automatic scans of data files for peak amplitude, area, latency, and slope within user-defined latency windows. All data and analyses can be exported to commercial statistical/graphical programs for the creation of publication-ready figures.

Amplifiers, Electronic↗

Hyperpolarizing and depolarizing GABAA receptor-mediated dendritic inhibition in area CA1 of the rat hippocampus.

1. gamma-Aminobutyric acidA (GABAA) receptor-mediated inhibition of pyramidal neuron dendrites was studied in area CA1 of the rat hippocampal slice preparation with the use of intracellular and extracellular recording and one-dimensional current source-density (CSD) analysis. 2. Electrical stimulation of Schaffer collateral/commissural fibers evoked monosynaptic excitatory postsynaptic potentials (EPSPs) and population EPSPs, which were followed by biphasic inhibitory postsynaptic potentials (IPSPs). In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV), stimulation in stratum radiatum evoked monosynaptic fast, GABAA and late, GABAB receptor-mediated IPSPs and fast and late positive field potentials recorded in s. radiatum. 3. Fast monosynaptic IPSPs and fast positive field potentials evoked in the presence of DNQX and APV were reversibly abolished by the GABAA receptor antagonist bicuculline methiodide (BMI; 30 microM) and were not changed by the GABAB receptor antagonist P-[3-aminopropyl]-P-diethoxymethylphosphinic acid (CGP 35,348; 0.1-1.0 mM). CGP 35,348 (0.1 mM) reversibly blocked late monosynaptic IPSPs and late positive field potentials. These results suggest that fast field potentials are GABAA receptor-mediated population IPSPs (GABAA, fast pIPSPs) and that late field potentials are GABAB receptor-mediated population IPSPs (GABAB, late pIPSPs). 4. Fast pIPSPs were reversibly abolished when the extracellular Cl- concentration [( Cl-]o) was reduced from 132 to 26 mM in parallel with a depolarizing shift in the reversal potential of fast IPSPs. Paired or repetitive stimulation in s. radiatum reversibly depressed fast pIPSPs and fast IPSPs. Paired-pulse depression of fast pIPSPs was reversibly antagonized by CGP 35,348 (0.4-0.8 mM). 5. Laminar analysis of s. radiatum-evoked fast pIPSPs and one-dimensional CSD analysis revealed active current sources in s. radiatum and passive current sinks in s. oriens and s. lacunosum moleculare. S. radiatum sources were abolished by pressure application of BMI in s. radiatum but not in s. oriens. Stimulation in s. oriens, s. pyramidale, or s. lacunosum moleculare evoked GABAA current sources horizontal to the stimulation site. Changes in the dendritic location of inhibitory current with changes in stimulus location paralleled changes in the distribution of excitatory current. 6. In the presence of 4-aminopyridine (50-100 microM), DNQX and APV long-lasting depolarizing GABAA receptor-mediated responses (LLDs) occurred spontaneously or could be evoked. Current sinks associated with s. radiatum-evoked LLDs were located in the same dendritic area as sources associated with hyperpolarizing fast IPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Two components of long-term potentiation induced by different patterns of afferent activation.

Long-term potentiation (LTP) of excitatory synaptic transmission could be a mechanism underlying memory. Induction of LTP requires Ca2+ influx into postsynaptic neurons through ion channels gated by NMDA (N-methyl-D-aspartate) receptors in hippocampus (area CA1 and dentate gyrus) and neocortex. Here we report that a component of LTP not requiring the activation of NMDA receptors can be induced in area CA1. The component is dependent on tetanus frequency, requires increases in postsynaptic intracellular Ca2+ concentrations, and is suppressed by an antagonist of voltage-dependent Ca2+ channels.

2-Amino-5-phosphonovalerate↗

Differential effects of NMDA receptor antagonist APV on tetanic stimulation induced and calcium induced potentiation.

Enduring synaptic potentiation can be induced in area CA1 of hippocampus by tetanic stimulation and by exposure to a medium containing high Ca2+ concentration. Both tetanic stimulation and high Ca2+ induce potentiation through voltage-dependent, post-synaptic mechanisms. Tetanus-induced long-term potentiation (LTP) was blocked by 50 microM D,L-2-amino-5-phosphonovalerate (APV) as previously reported by others. In contrast, Ca2(+)-induced long-lasting potentiation was not reduced by 50 microM APV. Thus the mechanisms by which tetanic stimulation and exposure to high Ca2+ induce synaptic potentiation may differ.

2-Amino-5-phosphonovalerate↗

Effects of extracellular potassium concentration and postsynaptic membrane potential on calcium-induced potentiation in area CA1 of rat hippocampus.

Long-lasting potentiation can be induced in area CA1 of hippocampus by a relatively brief (7-10 min) exposure to a higher (4.0 mM) than normal (2.0 mM) extracellular calcium concentration. We have found that long-lasting calcium-induced potentiation is dependent on extracellular potassium concentration. Slices exposed to high extracellular calcium in the presence of normal extracellular potassium (3.35 mM) showed a transient facilitation. Long-lasting potentiation was induced by exposure to high calcium only in slices also exposed to higher than normal extracellular potassium (6.25 mM). In intracellular experiments we found that injection of depolarizing current into postsynaptic neurons could substitute for high extracellular potassium. These results suggest that calcium-induced potentiation involves a postsynaptic, voltage-dependent mechanism. A similar conclusion has been reached for tetanus-induced potentiation. We also found that calcium-induced potentiation, like tetanus-induced potentiation, is not accompanied by an increase in postsynaptic input resistance.

Action Potentials↗

Associative learning changes intrinsic to Hermissenda type A photoreceptors.

The eyes of the nudibranch mollusc Hermissenda have previously been shown to contain 2 classes of photoreceptors. Type B photoreceptors exhibit increased light responses and membrane excitability after repeated pairings of light and rotation and play an important role in the mediation of associatively produced reductions in phototactic behavior. Type A photoreceptors have also been shown to change with associative training. In previous research, Type A photoreceptors from trained animals were found to have reduced light responses. Because these recordings were obtained from synaptically intact cells, it was not possible to determine whether the effects of associative training reflected changes in synaptic input to Type A photoreceptors or intrinsic changes in somatic conductances. In the present study, intracellular recordings from synaptically isolated Type A photoreceptors were obtained on retention days after training, and pairing-specific decreases in light-induced generator potentials and decreases in resting input resistance were observed. Current- and voltage-clamp analysis of Type A photoreceptors from untrained animals revealed that an important determinant of the steady-state light response was a calcium-activated K+ current (IK-Ca). Thus, Type A photoreceptors also appear to be a primary site for associative information storage in Hermissenda. It is suggested that enhancement of IK-Ca by associative training may contribute to the diminished light response of Type A photoreceptors.

Accommodation, Ocular↗

Chemosensory conditioning of Hermissenda crassicornis.

Bite-strike responses of Hermissenda crassicornis, elicited by chemosensory stimulation of the lips, were found to be modified when food extracts were paired with rotation-produced stimulation of the statocysts. Animals that received repeated pairings of an extract of 1 food (conditioned stimulus, CS) with rotation exhibited suppressed bite-strike responses to that food for up to 48 hr after training. This suppression was usually specific to the trained food and was pairing-specific as well. Discriminative conditioning was also demonstrated. Animals trained with 1 CS paired with rotation and a second CS that was unpaired (CS-) showed suppressed bite-strike responses to the first CS. The results demonstrate that Hermissenda can learn to avoid foods that reliably signal an aversive event and may allow an analysis of higher order conditioning phenomena.

Animals↗

Neurochemical and immunocytochemical studies of serotonin in the Hermissenda central nervous system.

In the preceding paper we showed that serotonin mimics the effects of associative conditioning on Type B photoreceptors of Hermissenda. Here we show that serotonin is present in the Hermissenda central nervous system, and that it is released in a calcium-dependent manner. A large number of serotonergic cell bodies are present in the cerebropleural ganglia (CPG). Cell bodies in the CPG are located in three small, symmetrical clusters. One cluster (2-3 cells) located at the anterior end of the CPG contains a large cell that projects to the buccal ganglion. A second cluster (2-3 cells) is located posterior to the first and near the midline of the nervous system. A third cluster (1-2 cells) was located slightly more posteriorly than the second. Type B photoreceptors and the S/E optic ganglion cell project to a region of the CPG neuropil which is heavily innervated by serotonin immunoreactive fine processes. Since serotonin mimicked the effects of associative conditioning on Type B cells, and is present in an appropriate region of the CPG neuropil, serotonin may mediate some effects of associative conditioning on Type B cells. Results supporting this hypothesis are presented in an accompanying paper.

Animals↗

Serotonin involvement during in vitro conditioning of Hermissenda.

To determine if serotonin may be involved in associative conditioning-produced changes in the excitability and photoresponses of Type B photoreceptors, isolated nervous systems were exposed to an in vitro conditioning procedure in the presence or absence of drugs that alter normal serotonergic neurotransmission. Pairings of light and intracellular depolarization of a caudal hair cell (in vitro conditioning) produced a pairing-specific depolarization of Type B photoreceptors that was accompanied by an increase in resting input resistance. Treatment of nervous systems with pharmacological agents which disrupt 5-HT neurotransmission attenuated membrane potential and input resistance changes of Type B photoreceptors. These drugs included serotonin uptake inhibitors (imipramine, fluoxetine), a receptor antagonist (bufotenine), and a neurotoxin (5,7-dihydroxytryptamine; 5, 7-DHT). Yohimbine, an alpha 2-receptor antagonist, was without effect. These results, and those in the accompanying papers, suggest that serotonin modulates Type B photoreceptor excitability during associative conditioning.

5,7-Dihydroxytryptamine↗

Temporal order sensitivity of associative neural and behavioral changes in Hermissenda.

Hermissenda's neural and behavioral changes produced by light-rotation pairings were assessed as a function of the temporal relations between visual and vestibular stimulation. The results of in vitro simulations of conditioning indicated that simultaneous pairings (synchronous onsets and offsets of light and caudal hair cell stimulation) resulted in significantly greater cumulative depolarization of Type B photoreceptors than did either forward (light preceded hair cell stimulation) or backward (hair cell stimulation preceded light) pairings. Further experiments revealed that the attenuation of cumulative depolarization produced by the forward and backward pairings reflected the asynchrony of stimulus offsets that characterize these conditioning sequences, rather than their onsets. Analogous behavioral experiments revealed that intact animals trained with forward or backward pairings exhibited significantly less conditioning than those trained with simultaneous pairings. Strong parallels between the magnitude of cumulative depolarization from in vitro conditioning studies and the behavioral results for intact animals were also observed in experiments in which stimulus onset synchrony was held constant but offsets were made asynchronous, and vice versa. Thus Hermissenda exhibits a sensitivity to the temporal arrangement of light and rotation, and the results of behavioral conditioning can be predicted accurately from the outcome of in vitro conditioning of the isolated nervous system.

Animals↗